J. Am. Chem. Soc., 129 (17), 5462 -5471, 2007. 10.1021/ja067819i S0002-7863(06)07819-X
Web Release Date: April 11, 2007

Copyright © 2007 American Chemical Society

Hierarchical Assembly of Model Cell Surfaces: Synthesis of Mucin Mimetic Polymers and Their Display on Supported Bilayers

David Rabuka, Raghuveer Parthasarathy, Goo Soo Lee, Xing Chen, Jay T. Groves, and Carolyn R. Bertozzi*

Contribution from the Departments of Chemistry, Molecular and Cell Biology, and Howard Hughes Medical Institute, University of California, and Materials Sciences Division and The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720

crb@berkeley.edu

Received November 1, 2006

Abstract:

Molecular level analysis of cell-surface phenomena could benefit from model systems comprising structurally defined components. Here we present the first step toward bottom-up assembly of model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial membranes. Natural mucins are densely glycosylated O-linked glycoproteins that serve numerous functions on cell surfaces. Their large size and extensive glycosylation makes the synthesis of these biopolymers impractical. We designed synthetically tractable glycosylated polymers that possess rodlike extended conformations similar to natural mucins. The glycosylated polymers were end-functionalized with lipid groups and embedded into supported lipid bilayers where they interact with protein receptors in a structure-dependent manner. Furthermore, their dynamic behavior in synthetic membranes mirrored that of natural biomolecules. This system provides a unique framework with which to study the behavior of mucin-like macromolecules in a controlled, cell surface-mimetic environment.


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